As one of the world’s only nonprofit biotech companies, the ALS Therapy Development Institute (ALS TDI) is a unique organization – a lab that is funded by the community and 100% dedicated to ending ALS. We serve as a “drug-discovery engine” for ALS – meaning we utilize our experienced team and our established and innovative research programs to advance treatments into human clinical development. We work to invent and discover treatments in our own lab, while also helping to push the pace of research forward in partnership with others – all with the ultimate goal of getting more high-quality drug leads into human trials.

ALS TDI has helped several treatments advance from the lab and into clinical trials, and we are optimistic that there will be many more. Below we discuss three recent examples.

Drug Discovery and AT-1501

Our primary path toward achieving this goal is working to invent treatments ourselves through our industry-leading drug discovery programs. One of the proudest achievements in the history of ALS TDI so far is the invention of AT1501, an ALS treatment that is now in Phase 2 clinical trials. AT-1501 is a novel antibody which acts in a highly targeted, disease-specific way to modulate the immune system. ALS TDI is the first, and so far the only nonprofit biotech to invent an ALS treatment and advance it to clinical trials.

After being invented at ALS TDI, AT-1501 was advanced through clinical trials by Anelixis Therapeutics, a for-profit clinical-stage development company. In 2019, Anelixis successfully completed phase 1 trials of AT-1501. In 2020, Anelixis was acquired by Novus Therapeutics (now Eledon Pharmaceuticals), a publicly traded company. A phase 2 study is currently recruiting.

Drug Validation: Helping our Partners Advance Promising Treatments

While our major focus is on the invention of completely new ALS treatments, we also allocate time and resources toward investigating the validity of promising results found in experiments by other researchers and companies. We do this by trying to replicate the experiments that were conducted in these other labs and testing to see if our experiments produce the same results. In drug discovery, this process is known as “validation.”

Often, our validation efforts result in finding that a drug is not as promising as previous results may have indicated – a disappointing result, but one that can help prevent researchers and pALS from wasting time in a trial that will ultimately fail. However, when we are able to successfully reproduce the results from an experiment, or demonstrate additional promising results, we can help strengthen the case for that treatment to reach clinical trials in humans.

ALS TDI’s Role in Advancing Copper ATSM

One such drug that we helped validate is Copper ATSM (CuATSM), developed by Collaborative Medicine Development, LLC. CuATSM is a small molecule therapy that serves as a “copper chaperone,” allowing the body to more safely absorb elemental copper that is normally toxic. Copper is an essential element to the function of human cells, and there is evidence that a copper dysregulation may be a contributing factor in at least some forms of ALS, as well as other neurodegenerative diseases. While early studies of CuATSM showed promising results for ALS, ALS TDI’s preclinical validation of the drug in 2016 helped move it into an ultimately successful Phase 1 trial. A Phase 2/3 trial is currently recruiting in Australia.

According to Dr. Peter Crouch, who conducted early preclinical experiments with CuATSM at the University of Melbourne, the validation by ALS TDI helped to raise excitement and interest in CuATSM as a potential ALS treatment.

“That was at the stage when we'd already published quite a few papers on the topic,” he says. “But I think it's fair to say that they weren't really registering with a broader audience. So, when the ALS TDI paper came out, that's when people started paying more attention to this particular compound as a potential option.”

ALS TDI’s Role in Advancing AP 101

Another drug the ALS TDI helped validate is AP-101. AP-101 is a monoclonal antibody that targets the “misfolded” SOD1 protein produced by the mutated SOD1 gene, one of the most common causes of familial ALS. Antibodies are proteins that are normally produced by the immune system and bind to and neutralize foreign pathogens – like disease-causing bacteria and viruses – in the body. A monoclonal antibody is an antibody produced by a cloned immune cell. They can be designed to bind to a specific protein – in the case of AP-101, misfolded SOD1 proteins in motor neurons.

ALS TDI collaborated with AP 101’s original developer, Neurimmune, in 2013. ALS TDI researchers saw encouraging results after testing the drug in our SOD1 mouse model of ALS, contributing to the collection of data that was essential for moving it into a Phase 1 trial that began enrolling in 2019 and is still ongoing.

The Future: More Drugs Advanced Into More Trials

In addition to these drugs that have reached trials, ALS TDI continues to work toward advancing more treatments from the lab to the clinic. We are currently pursuing two promising discoveries with the potential to help people living with ALS – a new target for C9orf72-associated ALS and a series of drug compounds that have shown promise in our induced pluripotent stem cell models of ALS.

The future of these potential ALS treatments depends on your support – as a nonprofit biotech, we rely on the generosity of our donors and community members to fund our essential research. To learn more about what we’re working on – and how you can support it – click here.